Pigmentation Pattern of Iris and Fundus in 75 Chinese Families With GPR143-Associated Ocular Albinism

Ocular albinism is an X-linked recessive genetic disorder that exhibits highly heterogeneous phenotypes involving significant visual deficits and pigmental changes in the eye due to GPR143 variants. The aim of this study is to describe the phenotypic spectra of patients with ocular albinism based on the identification of GRP143 variants in a large Chinese cohort.

GPR143 variants were selected from an in-house data set. Potential pathogenic variants were evaluated using multiple bioinformatic analyses and validated by Sanger sequencing. Clinical data of individuals with likely pathogenic variants in GPR143 were thoroughly analyzed.

Forty-six hemizygous variants (18 missense, 8 stop-gain, 8 splicing, 5 frameshift, 6 deletion, and 1 in-frame insertion), including 31 novel ones, were detected in 75 probands with ocular albinism. Three distinct patterns of iris pigmentation and three grades of fundus pigmentation were classified according to available data of the 75 families. Pattern II of iris, characterized by hyperpigmentation in the peripupillary area, was the most prevalent, with involvement of 41.2% of patients. Approximately 52.1% of patients exhibited atypical pigment changes in both the iris and the fundus. Patients with grade 3 fundus, characterized by pronounced depigmentation in the macular region, exhibited significantly poorer best-corrected visual acuity compared to those with other grades (P = 0.0031). Follow-up examinations indicated that fundus pigment deposition increased with age during early childhood.

This study expands the variant spectrum of GPR143 and clarifies phenotypic features of ocular albinism, facilitating diagnosis. Hyperpigmentation in the peripupillary area suggests a complex role of GPR143 in melanosome production.